Modeling sporadic Alzheimer's disease using brain organoids: Emerging trends and translational opportunities

Sporadic form of Alzheimer's disease (sAD), remains a complex neurodegenerative disorder with limited translational models. Brain organoids derived from human induced pluripotent stem cells (hiPSCs) have emerged as promising tools to recapitulate aspects of human brain development and pathology. Recent advances have introduced vascularized, immune-competent organoids capable of modeling hallmark features of sAD, including amyloid-β accumulation, tau pathology, and neuroinflammation. New strategies to enhance organoid maturation, cellular diversity, and aging phenotypes are pushing the boundaries of disease modeling. This review highlights cutting-edge developments in brain organoid systems for studying sAD, addresses key limitations, and outlines future directions to improve their translational relevance for therapy and mechanistic insights.